What are the management options for orthostatic hypotension in a patient with HFrEF on sacubitril/valsartan and nebivolol?

Management Options for Orthostatic Hypotension in HFrEF Patients on Sacubitril/Valsartan and Nebivolol

For patients with HFrEF experiencing orthostatic hypotension while on sacubitril/valsartan and nebivolol, dose reduction of these medications rather than discontinuation is the preferred approach to manage symptoms while maintaining mortality benefit. 1

Assessment and Initial Management

• Confirm orthostatic hypotension: Measure blood pressure in supine position and after standing for 1-3 minutes; a drop in systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg confirms the diagnosis
• Evaluate severity: Assess for symptoms (lightheadedness, dizziness, syncope) and impact on quality of life
• Review medication timing: Consider spacing sacubitril/valsartan and nebivolol administration to avoid peak hypotensive effects occurring simultaneously

Stepwise Management Approach

Step 1: Non-Pharmacological Interventions

• Increase fluid intake (2-3 liters daily unless fluid restricted)
• Increase salt intake (unless contraindicated)
• Compression stockings to reduce venous pooling
• Avoid rapid position changes, especially in the morning
• Elevate head of bed by 30° at night to reduce nocturnal diuresis
• Avoid alcohol and large meals which can worsen hypotension

Step 2: Medication Adjustments

1. Sacubitril/valsartan adjustment:

   • Consider reducing dose to intermediate (49/51 mg BID) or minimum dose (24/26 mg BID) 2, 3
   • Studies show that even reduced doses maintain clinical benefit with fewer hypotensive effects 3
   • Do not discontinue completely as this medication provides significant mortality benefit

2. Nebivolol adjustment:

   • Consider reducing dose or switching to a less vasodilating beta-blocker (e.g., metoprolol succinate)
   • Target lower end of dose range while maintaining heart rate control

3. Diuretic management:

   • Reduce or temporarily discontinue diuretics if euvolemic
   • Consider switching to evening administration to minimize daytime hypotension

Step 3: Additional Pharmacological Options

If orthostatic hypotension persists despite above measures:

• Midodrine: Start with 2.5 mg TID (morning, noon, and mid-afternoon but not after 6 PM); can increase to 10 mg TID
• Fludrocortisone: Start with 0.1 mg daily; can increase to 0.2 mg daily with careful monitoring of potassium and fluid status
• Droxidopa: Consider for severe cases (100 mg TID, titrated up to 600 mg TID as needed)

Special Considerations

• Monitoring: Check renal function, electrolytes, and blood pressure (both supine and standing) regularly during medication adjustments
• Caution with MRAs: If patient is on spironolactone or eplerenone, monitor closely for hyperkalemia when adjusting other medications 4
• SGLT2 inhibitors: If patient is on an SGLT2 inhibitor, consider temporary discontinuation until orthostatic hypotension is controlled 1

When to Consider Specialist Referral

• Persistent severe symptoms despite above measures
• Significant decline in renal function with medication adjustments
• Recurrent syncope or falls due to orthostatic hypotension

Pitfalls to Avoid

• Complete discontinuation of guideline-directed medical therapy: This increases mortality risk; dose reduction is preferred over discontinuation 1
• Overdiuresis: Excessive diuresis can worsen orthostatic hypotension
• Alpha-blockers: Avoid adding alpha-blockers like doxazosin as they can worsen orthostatic hypotension in HF patients 4
• Non-dihydropyridine calcium channel blockers: Verapamil and diltiazem are contraindicated in HFrEF and can worsen heart failure 4, 1

The evidence strongly supports maintaining sacubitril/valsartan therapy even at reduced doses rather than discontinuing it, as studies show continued benefit with fewer hypotensive effects 3, 5. Similarly, beta-blockers should be maintained at the highest tolerated dose as they provide significant mortality benefit in HFrEF patients 1.